THE ANTIPROLIFERATIVE EFFECT OF THE PINEAL HORMONE, MELATONIN, ON HUMAN BREAST CANCER CELLS IN VITRO.

Abstract

There is some evidence to suggest that the pineal gland influences neoplastic growth. Either crude or partially purified pineal extracts have been used to treat malignant neoplasms in humans. More compelling evidence indicates that the pineal hormone melatonin, in addition to its well-known antireproductive effects, may also exert oncostatic effects particularly in animal models of human breast cancer. The purpose of this study was to examine a possible direct action of melatonin on the growth morphology and physiology of human breast cancer cells in vitro. Studies are described in which physiological concentrations of melatonin are shown to have markedly inhibitory effects directly on MCF-7 human breast cancer cells grown in culture. This antimitotic effect is not observed in MCF-7 cells at supra- or subphysiological concentrations of melatonin. This growth-inhibitory effect appears to be tissue specific since fibroblastic cells were not affected by melatonin. Other pineal indoles failed to inhibit the proliferation of this human breast cancer cell line, suggesting that this growth-inhibitory effect is specific for melatonin and is not a general characteristic shared among the family of pineal indoles. Reductions in media serum concentrations dramatically suppressed the response of cells to melatonin's inhibitory action. Serum values of 2.5 percent or lower resulted in a loss of melatonin's action as did growing the cells in serum-free medium or medium containing charcoal-treated serum. It appears that certain serum factors are necessary for these cells to respond to melatonin's antiproliferative action. Melatonin, when added to cells grown in media supplemented with 10 percent fetal calf serum decreased the synthesis of proteins and resulted in morphological alterations suggestive of a sublethal toxic injury. Melatonin appears to have a direct role in inhibiting the proliferation of breast cancer cells; however, the presence of melatonin per se does not seem to be the fundamental cause of this antimitotic action since no activity is observed when cells are propagated in media containing charcoal-treated fetal calf serum or serum-free medium. There appears to be a requirement for certain serum factors in this antiproliferative action. Two factors that have proved important in this process are the hormones estradiol and prolactin. (Abstract shortened with permission of author.)